was used due to evidence from twin studies that a large proportion of genetic liability is shared across substances (Kendler et al., 2003; Agrawal et al., 2012) and the use of a similar factor score in a prior GWAS (Wetherill et al., 2015). Because substance use disorders are highly comorbid with other forms of psychopathology (Swendsen et al., 2010; Hasin and Kilcoyne, 2012), with evidence of shared genetic and environmental risk factors (Kendler et al., 2003; Agrawal et al., 2012), we hypothesized that increased cross-disorder polygenic risk would be associated with greater general substance involvement. Next, we tested individual associations between PRS for each of the five psychiatric disorders included in the cross-disorder meta-analysis (ADHD, AUT, BIP, MDD, and SCZ) and involvement with the five substances assessed in SAGE (alcohol, cannabis, cocaine, opioids, and nicotine). Finally, we tested whether these associations were substance-specific or best explained by association with the general substance involvement factor.
